The delivery of therapeutic material, such as genetic material, into tissue has a wide range of useful applications including vaccination, replacement of a defective gene, DNA immunization, introduction of an immunogen, anti-sense therapy, and miRNA, RNAi, aptamer, or siRNA therapy. For instance, nucleic acids, such as DNA, for example, can be injected into tissue, wherein the nucleic acids are taken up by the surrounding cells albeit inefficiently. DNA introduced in this manner will produce the protein that the DNA encodes. The successful delivery of nucleic acids into tissue and the uptake of the nucleic acids by the cells is difficult, especially when significant amounts of protein expression are desired (e.g., as is desired for DNA-based vaccination). Conventional injection of genetic material into tissue generally results in poor uptake by the cells and low levels of protein expression, if any at all.
Gene therapy is an important tool in the future for treatment of human and animal disease. Some clinical progress has been made in recent years with one example of a patient with partial restoration of vision following gene therapy (Bainbridge New Engl J Med. 2008 358(21):2231). A major area for clinical application of gene therapy is genetic vaccination for infectious diseases. However, a major limitation to make gene therapy a reality is the difficulty to reproducibly deliver the genetic material. Genes can be delivered either by viral vectors or in the form of plasmid DNA. Viral vectors have limitations in that they generate anti-vector responses that limit their repeated use, and they are expensive to produce and to store. DNA has the advantage that it does not induce anti-vector responses and is relatively cheap to produce and to store. However, the major problem with DNA is the poor uptake into human cells in vivo. Thus, new robust and tolerable ways for DNA delivery to human cells in vivo can accelerate the whole field of gene therapy.
Intravascular administration approaches have also been developed to deliver therapeutic agents to animals (see e.g., U.S. Pat. Nos. 6,379,966; 6,897,068; 7,015,040; 7,214,369; 7,473,419; and 7,589,059, all of which are hereby expressly incorporated by reference in their entireties). Intravascular administration can be very difficult to implement in practice; however, requiring skilled clinicians and, if performed incorrectly, the procedure can lead to punctured blood vessels, hematomas, and the development of internal blood clots, which could lead to an embolism. Furthermore, the intravascular administration approach can produce a wide dispersion of the introduced therapeutic agent (e.g., nucleic acid and protein), which is undesirable when trying to encourage the body to mount an immune response to the delivered agent. Accordingly, there remains a need for devices and methods that facilitate the delivery and uptake of therapeutic molecules such as nucleic acids and proteins.